Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2-targeted CAR-T cell therapy, in prostate cancer
Prostate cancer is generally considered an immunologically “cold” tumor type that is insensitive to immunotherapy. Targeting surface antigens on tumors through cellular therapy can induce a potent antitumor immune response to “heat up” the tumor microenvironment. However, many antigens expressed on prostate tumor cells are also found on normal tissues, potentially causing on-target, off-tumor toxicities and a suboptimal therapeutic index. Our studies revealed that six-transmembrane epithelial antigen of prostate-2 (STEAP2) was a prevalent prostate cancer antigen that displayed high, homogeneous cell surface express...
Source: Journal of Clinical Investigation - November 15, 2023 Category: Biomedical Science Authors: Peter Zanvit, Dewald van Dyk, Christine Fazenbaker, Kelly McGlinchey, Weichuan Luo, Jessica M. Pezold, John Meekin, Chien-ying Chang, Rosa A. Carrasco, Shannon Breen, Crystal Sao-Fong Cheung, Ariel Endlich-Frazier, Benjamin Clark, Nina J. Chu, Alessio Van Source Type: research
Initial productive and latent HIV infections originate in vivo by infection of resting T cells
Productively infected cells are generally thought to arise from HIV infection of activated CD4+ T cells, and these infected activated cells are thought to be a recurring source of latently infected cells when a portion of the population transitions to a resting state. We discovered and report here that productively and latently infected cells can instead originate from direct infection of resting CD4+ T cell populations in lymphoid tissues in Fiebig I, the earliest stage of detectable HIV infection. We found that direct infection of resting CD4+ T cells was correlated with the availability of susceptible target cells in ly...
Source: Journal of Clinical Investigation - November 15, 2023 Category: Biomedical Science Authors: Stephen W. Wietgrefe, Jodi Anderson, Lijie Duan, Peter J. Southern, Paul Zuck, Guoxin Wu, Bonnie J. Howell, Cavan Reilly, Eugène Kroon, Suthat Chottanapund, Supranee Buranapraditkun, Carlo Sacdalan, Nicha Tulmethakaan, Donn J. Colby, Nitiya Chomchey, Pee Source Type: research
Type I interferon signature and cycling lymphocytes in macrophage activation syndrome
CONCLUSION MAS associated with SD is characterized by overproduction of IFN-I, which may act in synergy with IL-15 to generate CD38+HLA-DR+ cycling lymphocytes that produce IFN-γ. (Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - November 15, 2023 Category: Biomedical Science Authors: Zhengping Huang, Kailey E. Brodeur, Liang Chen, Yan Du, Holly Wobma, Evan E. Hsu, Meng Liu, Joyce C. Chang, Margaret H. Chang, Janet Chou, Megan Day-Lewis, Fatma Dedeoglu, Olha Halyabar, James A. Lederer, Tianwang Li, Mindy S. Lo, Meiping Lu, Esra Meidan, Source Type: research
Reducing branched-chain amino acids improves cardiac stress response in mice by decreasing histone H3K23 propionylation
Identification of branched-chain amino acid (BCAA) oxidation enzymes in the nucleus led us to predict that they are a source of the propionyl-CoA that is utilized for histone propionylation and, thereby, regulate gene expression. To investigate the effects of BCAAs on the development of cardiac hypertrophy and failure, we applied pressure overload on the heart in mice maintained on a diet with standard levels of BCAAs (BCAA control) versus a BCAA-free diet. The former was associated with an increase in histone H3K23-propionyl (H3K23Pr) at the promoters of upregulated genes (e.g., cell signaling and extracellular matrix gen...
Source: Journal of Clinical Investigation - November 15, 2023 Category: Biomedical Science Authors: Zhi Yang, Minzhen He, Julianne Austin, Danish Sayed, Maha Abdellatif Source Type: research
CAP2 promotes gastric cancer metastasis by mediating the interaction between tumor cells and tumor-associated macrophages
In this study, we demonstrated that cyclase-associated protein 2 (CAP2) was upregulated in GC, especially in cases with lymph node metastasis, and was correlated with a poorer prognosis. The transcription factor JUN directly bound to the promoter region of CAP2 and activated CAP2 transcription. The N-terminal domain of CAP2 bound to the WD5 to WD7 domains of receptor for activated C kinase 1 (RACK1) and induced M2 macrophage polarization by activating the SRC/focal adhesion kinase (FAK)/ERK signaling pathway, which resulted in IL-4 and IL-10 secretion. Polarized M2 macrophages induced premetastatic niche formation and prom...
Source: Journal of Clinical Investigation - November 1, 2023 Category: Biomedical Science Authors: Guohao Zhang, Zhaoxin Gao, Xiangyu Guo, Ranran Ma, Xiaojie Wang, Pan Zhou, Chunlan Li, Zhiyuan Tang, Ruinan Zhao, Peng Gao Source Type: research
